Quantitative subcellular secondary ion mass spectrometry (SIMS) imaging of boron-10 and boron-11 isotopes in the same cell delivered by two combined BNCT drugs: in vitro studies on human glioblastoma T98G cells

• Published in: Radiation research Vol. 157; no. 6; p. 700
• Main Authors: Chandra, Subhash, Lorey II, Daniel R, Smith, Duane R
• Format: Journal Article
• Language: English
• Published: United States 01.06.2002
• Subjects: Borohydrides - metabolism; Borohydrides - pharmacology; Boron - analysis; Boron - metabolism; Boron Compounds - metabolism; Boron Compounds - pharmacology; Boron Neutron Capture Therapy; Cell Division - drug effects; Cell Division - radiation effects; Cell Size; Glioblastoma - pathology; Glioblastoma - therapy; Humans; Organelles - drug effects; Phenylalanine - analogs & derivatives; Phenylalanine - metabolism; Phenylalanine - pharmacology; Radioisotopes - analysis; Radioisotopes - metabolism; Spectrometry, Mass, Secondary Ion - methods; Sulfhydryl Compounds - metabolism; Sulfhydryl Compounds - pharmacology; Time Factors; Tumor Cells, Cultured
• ISSN: 0033-7587
• DOI: 10.1667/0033-7587(2002)157[0700:QSSIMS]2.0.CO;2

Ion microscopy was used for subcellular quantitative imaging of the isotopes 10B and 11B in the same cell to evaluate boron delivery using a mixture of two neutron capture therapy drugs, p-boronophenylalanine-fructose (BPA-F) and sodium borocaptate (BSH). The application of 10B-labeled BPA-F and 11B-labeled BSH allowed independent imaging of both 10B and 11B in the same cell using a CAMECA IMS-3f ion microscope. Mixed-drug treatments were compared to single-drug exposures given under identical conditions. 10BPA-F delivered 10B heterogeneously to T98G human glioblastoma cells, with a significantly reduced concentration in an organelle-rich perinuclear region. The intracellular distribution of 11B from 11BSH contrasted with that of the 10B from 10BPA-F, with 11B distributed nearly homogeneously throughout cells. The subcellular distributions of 10B and 11B were sustained in mixed-drug treatments and resembled their localizations after the single-drug treatments. In both single- and mixed-drug treatments, cellular levels of 10B from 10BPA-F nearly doubled between 1 h and 6 h, with a 3:1 intracellular to nutrient medium partitioning, while cellular levels of 11BSH remained essentially unchanged. The net effect of the combined treatment with 10BPA-F and 11BSH was an additive delivery of boron to cells. This study introduces a novel approach for checking potential synergistic, antagonistic or simple additive delivery of two mixed boronated compounds in cellular/subcellular compartments.